The cellular events in gastric mucosal healing will be studied using morphological techniques. Preliminary studies from this laboratory have shown that ethanol produces maximal tissue damage by 8 min. after its instillation. This damage is both focal where hyperemia occurs and generalized where the apical portions of gastric glands are destroyed. By 8 min., healing has started as the necrotic tissue has sloughed off and the remaining viable cells have started migrating over the damaged glands to reseal the gastric mucosal barrier. This process continues for at least 1 hour when most of the mucosa has healed. Emphasis of this proposal is placed on the mechanisms of this rapid reepithelization. The specific aims of this study are to: 1) Document by morphological techniques the early sequence of events (30 seconds to 8 min.) in gastric mucosal injury with ethanol. 2) Determine what changes exogenously administrered prostaglandin pretreatment has on the mucosa so that it prevents the hyperemic areas produced by ethanol (cytoprotection). 3) Document the steps in rapid repithelization of the ethanol damaged mucosa as well as the long-term fate of the hyperemic areas in the stomach. 4) Determine whether the rapid reepithelization and repair of the mucosa can be accelerated by exogenously administered a) prostaglandins (PG), b) fibronectin, c) epidermal growth factor. Intragastric injections of ethanol will be given to fasted rats to damage the gastric mucosa. The stomach will be fixed for light and electron microscopy (em) from 30 sec. to 8 min. thereafter . PG will be given in a separate group of rats and the stomach fixed for em to help determine how PG prevents hyperemia. Rats with damaged mucosae will receive PG, or fibronectin, or epidermal growth factor and the stomach will be fixed at varying times to determine if they accelerate healing. The results of these experiments should help our understanding of the healing process as well as determine if it can be altered by substances shown to accelerate epithelial repair in other tissues. Hopefully, light will be shed on the causative factors of gastritis, hemorrhage, and ulceration and ultimately we hope to manipulate the healing process.